Table 2.

Positive and negative aspects of phage therapy [19,22,26,37,49,56,59,64,66,67,70,81,96,98,102,112,130,133].

Phage Therapy
Major Advantages	Description/Comments
Safe and effective bactericidal agents	Bacteria successfully infected with lytic phages are killed, which prevents the evolution of bacterial resistance.
Low inherent toxicity	Inherently non-toxic phages despite the presence of proteins and nucleic acids.
Auto “dosing”	Establishing the phage dose by the phages themselves depending on the density of the bacterial host.
Minimal disruption of commensal microflora	The high level of phage host specificity limiting damage to other bacterial species and genera.
No cross-resistance to antibiotics	Efficient clearance and treatment of bacterial infections resistant to antibiotics.
Various formulations and administration of phages	Monophages, cocktails, microneedle-based phages, liposomes, polymers, and electrospun fibers—encapsulated phages.
Immune tolerance	Interactions with the immune system of mammals result in the formation of a strain-specific mucosal phage barrier as a host’s defense against bacterial invasion.
Low costs	Relatively low production costs with technology improvement.
Phage-Antibiotic Synergy (PAS)	Synergistic phage-antibiotic combinations stimulating virulent phage growth.
Alternative treatment to antibiotics	The treatment of patients with renal impairment, allergy to antibiotics, or immunodeficiency.
Personalized therapy	“Magistral phage medicines” produced at a pharmacy according to a physician’s prescription for individual patients.
Biofilm clearance	Lysis of bacterial layers within the biofilm structure and depolymerization of capsular and structural polysaccharides by depolymerases.
Potential disadvantages	Alternative solutions
Phage selection and safety	Requirements: “obligately lytic” phages (not temperate), unable to display lysogeny, released from infected cells via lysis, stable under typical storage conditions and temperatures, fully sequenced to confirm the absence of unwanted genes, e.g., toxins, to avoid modification of the bacterial genome, changes in their phenotype, and increased toxicity.
Phage host-range limitations	Narrow range of bacterial hosts (several strains/species) limiting treatment procedures. The possibility of using phage cocktails or a combination of phages and other antibacterial agents broadens the lytic spectrum of phage products in relation to the spectrum of individual phage types.
Phage resistance mutants	A frequent phenomenon that can result in therapy failure, which can be circumvented by the treatment methods indicated above and searching for new phages from the environment.
Phages as a not-unique pharmaceutical	Live biological agents based on proteins capable of evolving during production and use. For some phage therapy protocols, the use of highly purified phage preparations is required.
Anti-phage antibodies interfering with treatment	Possible influence of anti-phage antibodies on the results of therapy, depending on, e.g., the route of administration, dosing schedule and duration of treatment, and immunogenicity of phages.
Cultural unfamiliarity with phages	Misconception of phages as potential viral pathogens causing human diseases. Currently, several phage products have been classified as GRAS (Generally Regarded As Safe) by the FDA.